In
microscopic images of cells known as thymocytes, the protein SATB1
(gold) forms a cage-like network surrounding dense regions of chromatin
(blue).

The nucleus of a typical human cell is just millionths of a meter across,
yet the DNA inside is well over a meter long -- long enough to contain
the entire human genome. With DNA so tightly folded and packed, it's a
wonder any genes are accessible at all.

Terumi Kohwi-Shigematsu of Berkeley Lab's Life Sciences Division has
learned how the bundle of DNA and proteins called chromatin rearranges
itself to allow gene expression in cells known as thymocytes. The answer
involves two principles that have fascinated her since her school days:
biological structures and biochemical reactions.

When she was 16 her father, a Japanese official, moved their family from
Tokyo to the Washington, D.C. area. In high school there, she recalls,

"I was fascinated that living things could be
entirely made out of chemicals."

She majored in chemistry at Washington College, then got her master's
degree in physical chemistry at Johns Hopkins University by using x-ray
crystallography to study DNA molecules. But because she wanted to "study
biological systems from broader angles, not restricted to the few molecules
that could be made into crystals" -- and because in living things
biological molecules interact dynamically -- she returned to Tokyo University
for graduate studies in biochemistry.

There, DNA's different forms focused her twin interests in chemistry
and structure. "At the time everyone assumed DNA remains double-stranded
in living cells, but I believed DNA is dynamic and takes other forms."

She was 24 years old, at the turning point of her career. Encouraged
by her thesis advisor, she proved that a simple chemical, chloroacetaldehyde
("It has a nice smell," she says, "but it can give you
lung cancer") reacts with single-stranded DNA and is an excellent
tool for examining protein-DNA reactions.

Meanwhile, in a neighboring lab, only one other graduate student, Yoshinori
Kohwi, was also dedicated enough to work through the hot summer months
without air conditioning. "We found each other alike, and we decided
to get married."

With Ph.D.s in hand, the newlyweds faced a problem. "Nori was offered
a tenured university position, but as a female in Japan I knew I would
not get an independent research position." She applied to the National
Institutes of Health and won a Fogarty Fellowship to study in the U.S.
Kohwi decided to accompany his wife to the Hutchinson Cancer Research
Center in Seattle, where both took postdoctoral positions.

When they later moved to the Burnham Institute in La Jolla, the institute
hired an immigration lawyer to help have her government visa's strict
requirement to return to Japan waived. "If I had returned,"
she says, "I would be a housewife by now."

After 13 years in La Jolla, Kohwi-Shigematsu and her husband decided
to explore a different research environment at Berkeley Lab. Here they
have worked both together and independently to unravel the secrets of
DNA.